CD138, which acts as a receptor for the extracellular matrix, is overexpressed on multiple myeloma (MM) cells and has been shown to influence MM cell development and/or proliferation. CD138 is also expressed on cells of ovarian carcinoma, cervical cancer (Numa et al., 2002), endometrical cancer (Choi et al., 2007), kidney carcinoma, gall bladder, transitional cell bladder carcinoma, gastric cancer (Wiksten et al. 2008), prostate adenocarcinoma (Zellweger et al., 2003), mammary carcinoma (Loussouarn et al., 2008) non small cell lung carcinoma (Shah et al., 2004), squamous cell lung carcinoma (Toyoshima et al., 2001), colon carcinoma cells and cells of Hodgkin's and non-Hodgkin's lymphomas, colorectal carcinoma (Hashimoto et al, 2008), hepato-carcinoma (Li et al., 2005), chronic lymphocytic leukemia (CLL), pancreatic (Conejo et al., 2000), and head and neck carcinoma (Anttonen et al., 1999) to name just a few.
The publications and other materials, including patents, used herein to illustrate the invention and, in particular, to provide additional details respecting the practice are incorporated by reference. For convenience, the publications are referenced in the following text by author and date and/or are listed alphabetically by author in the appended bibliography.
Tassone et al. (2004) reported excellent binding of the murine IgG1 antibody B-B4 to the CD138 antigen expressed on the surface of MM cells. Tassone also reported high cytotoxic activity of the immunoconjugate B-B4-DM1, which comprises the maytansinoid DM1 as an effector molecule, against multiple myeloma cells (see also US Patent Publ. 20070183971).
Ikeda et al. (2008 and 2009) reported promising in vitro results and results on xenograft models with the immunoconjugate BT062, which is based on B-B4.
While Tassone et al. and Ikeda et al. represent contributions to providing an effective treatment of MM and a composition of matter that may be employed in such a treatment, there remain a number of needs in the art.
There remains in particular a need to provide suitable treatment regimes for diseases associated with CD138 expression, including plasmaproliferative disorders associated with CD138 expression, such as MM. There more in particular remains a need for treatment regimes that ensure that toxicities towards non tumor cells, which also express CD138 are kept to a clinically acceptable level, either by employing only certain tolerable amounts of immunoconjugate and/or by combining the immunoconjugate with cytotoxic agents know to be effective against the disorder in question. There is also a need for treatment regimes that reduce the need for medications that are used to alleviate other symptoms of the disease.
This invention fulfills, in certain embodiments, one or more of these needs as well as other needs in the art which will become more apparent to the skilled artisan once given the following disclosure.